1046 RADIATION BIOLOGY 



accelerator of prothrombin conversion, (4) an effective antiheparin, and 

 (5) a contributor to the integrity of the capillary wall. In the absence of 

 platelets in animals exposed to massive doses of irradiation, hemorrhage- 

 gross or microscopic — may occur on the basis of failure of these functions. 

 The severity of hemorrhage will vary from animal to animal, however, 

 and local lesions such as ulcerations, abrasions, or systemic infection may 

 also affect the severity of the hemorrhagic manifestation. In general, 

 prothrombin studies of dogs (Allen et al., 1948) and rabbits (Jacobson, 

 Marks, Gaston, Allen, et al., 1948) subjected to total-body irradiation 

 in the LD 5 o range or above remained within normal limits except termi- 

 nally. It is generally agreed that the defects of increased bleeding time, 

 delayed clot retraction, and delayed prothrombin conversion result from 

 the thrombocytopenia. The delay in prothrombin conversion or con- 

 sumption can be corrected by addition of platelet-rich hemophilic dog 

 plasma but not by platelet-poor hemophilic dog plasma (Cronkite et al., 

 1950). The increased clotting time observed in dogs (Allen and Jacob- 

 son, 1947a, b; Allen et al., 1948), goats and swine (Cronkite, 1950), 

 rabbits (Jacobson, Marks, Gaston, Allen, et al., 1948), and guinea pigs 

 (Haley and Harris, 1949) may be related, in part or entirely, to platelet 

 reduction and delayed prothrombin conversion. Other factors known to 

 be concerned with clotting, such as fibrinogen and calcium blood levels, 

 are normal in irradiated animals. Allen and Jacobson (1947a) and Allen 

 et al. (1948) originally reported finding evidence for a heparin-like circulat- 

 ing anticoagulant in dogs exposed to 450 r which could usually be restored 

 to normal by administration of protamine sulfate or toluidine blue. 

 More recently Allen has found that, although after irradiation an increase 

 in the whole-blood clotting time (Lee- White) is usually demonstrable in 

 the dog, no evidence for a circulating heparin-like anticoagulant can be 

 demonstrated unless, in addition, transfusions have been given and 

 transfusion reactions have occurred. He has repeatedly called attention 

 to the discrepancy that is not infrequently observed between the platelet 

 number in the circulating blood and the whole-blood clotting time. He 

 has reported the appearance of a prolonged whole-blood clotting time 

 before platelets were appreciably reduced (Fig. 16-11) and a return of 

 whole-blood clotting time to normal a week or more before evidence of 

 platelet recovery could be detected in the peripheral blood. Although he 

 attributes this abnormality in whole-blood clotting principally to physio- 

 logic disturbances associated with thrombocytopenia, he believes that 

 other disturbances in the hemoplastic mechanism cannot be excluded at 

 this time. The role of increased capillary fragility in the hemorrhagic 

 syndrome induced by irradiation is probably of major importance. The 

 relation of thrombocytopenia in the causation of increased capillary 

 fragility is not understood nor has it been adequately explored. The fre- 

 quent association of petechial hemorrhage with thrombocytopenic states 



